Cannabidiol-enriched oil in children and adults with treatment-resistant epilepsy-does tolerance exist?

AIM: To evaluate the long-term effectiveness of cannabidiol (CBD)-enriched oil for the treatment of refractory epilepsy and to assess the development of tolerance to its anti-seizure effect. METHODS: A prospective study of 92 consecutive patients (age 1-37 years, mean-11.8 years) with treatment resistant epilepsy who were treated with cannabis oil extract (CBD/tetrahydrocannabinol [THC] ratio of 20:1). Mean monthly seizure frequency was reported by the patients/their parents during monthly clinic visits. Tolerance was defined as either the need to increase the dose by ≥30% due to reduced treatment efficacy or as an increase of ≥30% in mean monthly seizure frequency in patients treated for at least 3 months with no change in other anti-seizure medications. RESULTS: Mean follow-up time was 19.8 ± 12.5 months (range 3-45). Mean CBD dose was 11.3 (4-38) mg/kg/day. Twenty-nine (31%) patients discontinued treatment due to lack of effect or adverse reactions, which were reported in 51% (47/87) of the patients. Overall responder rate (>50% seizures reduction) was 54%, whereas 8 patients (9%) became seizure-free. Eighty-four patients were included in the tolerance analysis. Tolerance was observed in 21 (25%) patients after a mean duration of 7.3 ± 5.4 months of CBD-enriched oil treatment. There was a negative correlation between epilepsy duration and tolerance development (p = 0.038). CONCLUSIONS: We report for the first time the plausible appearance of tolerance to cannabidiol-enriched oil. This may limit treatment efficacy in the long-term clinical management of refractory epilepsy in both pediatric and adult population. Further studies are needed to investigate potential mechanisms.

Efficacy of CBD-enriched medical cannabis for treatment of refractory epilepsy in children and adolescents - An observational, longitudinal study.

The objective of this observational study was to evaluate the efficacy of medical cannabis for the treatment of refractory epilepsy. Fifty-seven patients (age 1-20 years) with epilepsy of various etiologies were treated with Cannabis oil extract (CBD/THC ratio of 20:1) for at least 3 months (Median follow up time-18 months). Forty-Six Patients were included in the efficacy analysis. Average CBD dose was11.4 mg/kg/d. Twenty-six patients (56%) had ≤50% reduction in mean monthly seizure frequency. There was no statistically significant difference in response rate among various epilepsy etiologies, and cannabis strain used. Younger age at treatment onset (<10 years) and higher CBD dose (>11 mg/kg/d) were associated with better response to treatment. Adverse reactions were reported in 46% of patients and were the main reason for treatment cessation. Our results suggest that adding CBD-enriched cannabis extract to the treatment regimen of patients with refractory epilepsy may result in a significant reduction in seizure frequency according to parental reports. Randomized controlled trials are necessary to assess its true efficacy.

Human milk fatty acids composition is affected by maternal age.

Human colostrums and transition milk were collected from women under the age of 37 years and women aged 37 years and older. Transition milk of the younger group had lower fat content and 10-fold higher concentrations of omega 6 FA, eicosadecanoic, and arachdonic acids. Gestational age affected the colostrum concentration of total fat and omega 3 and omega 6 FA composition only in the older group. We concluded that age may be a factor in the FA composition of human milk. This should be taken into account when planning diets for pregnant women of different ages.

The effect of advanced maternal age upon human milk fat content.

BACKGROUND: Little is known about the effect of maternal age on human milk (HM) composition. This study was designed to study fat content, estimated by creamatocrit (CMT), in HM collected in the first 2 weeks of life in older (≥ 35 years) compared with younger (<35 years) mothers. STUDY DESIGN AND METHODS: Ninety lactating mothers (48 older, 42 younger) of newborns were recruited within the first 3 days of delivery. CMTs were measured at 72 hours, 7 days, and 14 days after delivery for HM in a capillary tube after centrifugation at 5,366 g for 5 minutes. RESULTS: The groups did not differ in terms of maternal height and diet, infant birth weight, gestational age (GA), or pregnancy weight gain. They differed significantly in terms of maternal age and parity. Mean colostrum CMT was significantly higher in the group of older mothers. Colostrum CMT correlated positively with maternal age (R(2)=0.11, p=0.006) and inversely with GA (R(2)=0.1, p=0.03) but did not relate with either maternal weight or body mass index. CMT at age 7 days and 2 weeks was not affected by maternal age or GA. In multivariate regression analysis colostrum CMT correlated significantly only with maternal age and GA (R(2)=0.3, p<0.001). CONCLUSIONS: Colostrum fat content of older mothers is much higher than that of younger mothers and inversely related with GA at delivery. This increase in colostrum fat content obtained from mothers with advanced age may be due to increased fat synthesis and excretion in milk, reduced water content of milk, or a combination of both.